Dabigatran etexilate, a novel direct thrombin inhibitor, is a prodrug of dabigatran and is a non-peptide thrombin inhibitor. It was developed by Boehringer Ingelheim Pharmaceuticals, Inc. The oral drug is absorbed by the gastrointestinal tract and converts to dabigatran which has the direct anticoagulant activity. Dabigatran binds to the specific fibrin-binding sites of thrombin, preventing cleavage of fibrinogen to fibrin and blocking the final steps in the coagulation cascade network and thrombosis. Dabigatran can be dissociated from a fibrin-thrombin complex and play reversible anticoagulant effect. Dabigatran etexilate was first approved in Germany and England in April 2008. It was approved by the U.S. Food and Drug Administration (FDA) in October 2010 for reducing the risks of stroke or systemic embolism in patients with non-valvular atrial fibrillation. Currently, the approved dosage form is capsules with strengths of 75 mg and 150 mg, and the product name is Pradaxa®.
The chemical name of dabigatran etexilate is 3-[(2-{[4-(hexyloxycarbonylamino-imino-methyl)-pheny-lamino]-methyl}-1-methyl-1H-benzimidazol-5-carbonyl)-pyridin-2-yl-amino] propionic acid ethyl ester, having a formula of C34H41N7O5, a molecular weight of 627.74 and a chemical structural formula shown below (I):

Patent document WO98/37075 discloses the compound of dabigatran and its uses. Patent documents CN1638771A and WO03/074056A1 disclose a composition of dabigatran, and the composition contains the following main components: a core material consisting of an organic acid, an insulating layer and an active substance layer.
The patent document CN103127109A discloses a dabigatran etexilate composition containing the following main components: a core material containing the active substance, an insulating layer and an organic acid layer.
The present inventors discovered that in the composition prepared according to WO03/074056A1, since the active drug substance is in the outer layer of the pellet, the active drug is more prone to phase transformation and degradation. The present inventors also discovered that the composition prepared according to the patent document CN103127109A has a similar dissolution rate to that of a reference preparation (prepared according to CN1638771A) in the acid dissolution medium. However, in water, their dissolution rates are too different to be considered as to be similar in terms of in vitro dissolution.
In view of the problems in the prior arts, it is very important to develop a novel orally administered form of dabigatran etexilate or its pharmaceutical acceptable salts with more advantageous features.